TY - JOUR
T1 - Vagal nerve stimulation preserves right ventricular function in a rat model of right ventricular pressure overload
AU - Yoshida, Keimei
AU - Saku, Keita
AU - Jan Bogaard, Harm
AU - Abe, Kohtaro
AU - Sunagawa, Kenji
AU - Tsutsui, Hiroyuki
N1 - Funding Information:
Keita Saku received research funding from Omron Healthcare Co., Abiomed Japan K.K., NTT research, Inc., Asahi Kasei ZOLL Medical Corporation and Zeon Medical Inc., and honoraria from Abiomed Japan K.K. and Ono Pharmaceutical Co., Ltd. The remaining authors declare no conflict of interest.
Funding Information:
The authors thank Takuya Akashi for his technical support. This work was supported by the research program of Japan Agency for Medical Research and Development (20he1302033j0002, 22hk0102085h0201), Grants‐in‐Aid for Scientific Research (22K08222) from the Japan Society for the Promotion of Science, Japan Heart Foundation/Bayer Yakuhin Research Grant Abroad, Intramural Research Fund for Cardiovascular Diseases of National Cerebral and Cardiovascular Center (20‐6‐1, 21‐6‐7, 21‐2‐9), and the research grant from NTT research, Inc.
Publisher Copyright:
© 2022 The Authors. Pulmonary Circulation published by John Wiley & Sons Ltd on behalf of Pulmonary Vascular Research Institute.
PY - 2022/10
Y1 - 2022/10
N2 - Vagal nerve stimulation (VNS) ameliorates pulmonary vascular remodeling and improves survival in a rat model of pulmonary hypertension (PH). However, the direct impact of VNS on right ventricular (RV) function, which is the key predictor of PH patients, remains unknown. We evaluated the effect of VNS among the three groups: pulmonary artery banding (PAB) with sham stimulation (SS), PAB with VNS, and control (no PAB). We stimulated the right cervical vagal nerve with an implantable pulse generator, initiated VNS 2 weeks after PAB, and stimulated for 2 weeks. Compared to SS, VNS increased cardiac index (VNS: 130 ± 10 vs. SS: 93 ± 7 ml/min/kg; p < 0.05) and end-systolic elastance assessed by RV pressure–volume analysis (VNS: 1.1 ± 0.1 vs. SS: 0.7 ± 0.1 mmHg/μl; p < 0.01), but decreased RV end-diastolic pressure (VNS: 4.5 ± 0.7 vs. SS: 7.7 ± 1.0 mmHg; p < 0.05). Furthermore, VNS significantly attenuated RV fibrosis and CD68-positive cell migration. In PAB rats, VNS improved RV function, and attenuated fibrosis, and migration of inflammatory cells. These results provide a rationale for VNS therapy as a novel approach for RV dysfunction in PH patients.
AB - Vagal nerve stimulation (VNS) ameliorates pulmonary vascular remodeling and improves survival in a rat model of pulmonary hypertension (PH). However, the direct impact of VNS on right ventricular (RV) function, which is the key predictor of PH patients, remains unknown. We evaluated the effect of VNS among the three groups: pulmonary artery banding (PAB) with sham stimulation (SS), PAB with VNS, and control (no PAB). We stimulated the right cervical vagal nerve with an implantable pulse generator, initiated VNS 2 weeks after PAB, and stimulated for 2 weeks. Compared to SS, VNS increased cardiac index (VNS: 130 ± 10 vs. SS: 93 ± 7 ml/min/kg; p < 0.05) and end-systolic elastance assessed by RV pressure–volume analysis (VNS: 1.1 ± 0.1 vs. SS: 0.7 ± 0.1 mmHg/μl; p < 0.01), but decreased RV end-diastolic pressure (VNS: 4.5 ± 0.7 vs. SS: 7.7 ± 1.0 mmHg; p < 0.05). Furthermore, VNS significantly attenuated RV fibrosis and CD68-positive cell migration. In PAB rats, VNS improved RV function, and attenuated fibrosis, and migration of inflammatory cells. These results provide a rationale for VNS therapy as a novel approach for RV dysfunction in PH patients.
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U2 - 10.1002/pul2.12154
DO - 10.1002/pul2.12154
M3 - Article
AN - SCOPUS:85145186922
SN - 2045-8932
VL - 12
JO - Pulmonary Circulation
JF - Pulmonary Circulation
IS - 4
M1 - e12154
ER -